ArticleOncogene2000
Molecular dissection of TrkA signal transduction pathways mediating differentiation in human neuroblastoma cells.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 89 citations in OpenAlex.
- Article
- Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.Cell reports · 2024Article
- Identification of a novel gene signature for neuroblastoma differentiation using a Boolean implication network.Genes, chromosomes & cancer · 2023Article
- AC-265347 Inhibits Neuroblastoma Tumor Growth by Induction of Differentiation without Causing Hypocalcemia.International journal of molecular sciences · 2022Article
- Article
- RET receptor expression and interaction with TRK receptors in neuroblastomas.Oncology reports · 2020Article
- Molecular mechanism of nur77 gene expression and downstream target genes in the early stage of forskolin-induced differentiation in PC12 cells.Scientific reports · 2020Article
- WNT Signaling in Neuroblastoma.Cancers · 2019Review
- Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application.Journal of medicinal chemistry · 2019Article
- Ulk1 Governs Nerve Growth Factor/TrkA Signaling by Mediating Rab5 GTPase Activation in Porcine Hemagglutinating Encephalomyelitis Virus-Induced Neurodegenerative Disorders.Journal of virology · 2018Article
- WNT signaling, the development of the sympathoadrenal-paraganglionic system and neuroblastoma.Cellular and molecular life sciences : CMLS · 2018Review
- Cell death-based treatment of neuroblastoma.Cell death & disease · 2018Review
- ESM1 mediates NGFR-induced invasion and metastasis in murine oral squamous cell carcinoma.Oncotarget · 2016Article
- Retinoic acid-induced CHD5 upregulation and neuronal differentiation of neuroblastoma.Molecular cancer · 2015Article
- Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease.Human mutation · 2014Article
- Neuroblastoma in dialog with its stroma: NTRK1 is a regulator of cellular cross-talk with Schwann cells.Oncotarget · 2014Article
- Rotary bioreactor culture can discern specific behavior phenotypes in Trk-null and Trk-expressing neuroblastoma cell lines.In vitro cellular & developmental biology. Animal · 2014Article
- Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition.International journal of cancer · 2013Article
- FoxO3a negatively regulates nerve growth factor-induced neuronal differentiation through inhibiting the expression of neurochondrin in PC12 cells.Molecular neurobiology · 2013Article
- Network-based analysis of multivariate gene expression data.Methods in molecular biology (Clifton, N.J.) · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of the neurotrophin receptor TrkA by its ligand nerve growth factor (NGF) initiates a cascade of signaling events leading to neuronal differentiation in vitro and might play an important role in the differentiation of favorable neuroblastomas (NB) in vivo. To study TrkA signal transduction pathways and their effects on differentiation in NB, we stably expressed wild-type TrkA and five different TrkA mutants in the NGF unresponsive human NB cell line SH-SY5Y. Resulting clones were characterized by TrkA mRNA and protein expression, and by autophosphorylation of the receptor. Introduction of wild-type TrkA restored NGF responsiveness of SH-SY5Y cells, as demonstrated by morphological differentiation, activation of mitogen-activated protein kinases (MAPK) and induction of immediate-early genes. Expression of TrkA in the absence of NGF resulted in growth inhibition of transfectants compared to parental cells, whereas NGF-treatment increased their proliferation rate. Analysis of downstream signal transduction pathways indicated that NGF-induced differentiation was dependent on TrkA kinase activity. Our data suggest that several redundant pathways are present further downstream, but activation of the RAS/MAPK signaling pathway seems to be of major importance for NGF mediated differentiation of NB cells. Our results also show that the signaling effector SH2-B is a substrate of NGF-mediated Trk signaling in NB, whereas it is not activated by NGF in rat pheochromocytoma PC12 cells. This might explain the differences we observed in TrkA signaling between neuroblastoma and PC12 cells. Further insight into TrkA signaling may suggest new options for the treatment of NB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.